Spatial Genomics Tape Transfer Cryostat Microtome
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Solution Overview
Problem
Current methods for analyzing human tissue samples are wasteful and inefficient, as they require retrieving entire tissue blocks for sectioning, leading to waste of tissue and degradation of molecules during staining, and struggle to accurately map the three-dimensional structure of tumors due to heterogeneity of cell types.
Innovation Solution
A system using a tape transfer cryostat-microtome technique to generate sections with minimal distortion, allowing for precise spatial referencing and retrieval of specific microscopic regions within a three-dimensional tissue volume, enabling accurate histological, genomic, and transcriptomic analysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If the whole tissue block is retrieved for sectioning to examine a specific region, then the region of interest can be accessed, but the majority of the tissue is wasted
Solution Approach 1:
The tissue block is divided into multiple serial sections, each representing a specific z-coordinate plane. This segmentation allows the system to access only the specific section containing the region of interest rather than retrieving the entire block, thereby reducing tissue waste while maintaining spatial localization accuracy.
Solution Approach 2:
The patent introduces a three-dimensional coordinate system (x, y, z) where x and y represent horizontal positions on a section and z represents the vertical position corresponding to the section depth. This dimensional framework enables precise spatial referencing and allows retrieval of specific (x, y, z) locations without accessing the entire tissue block.
2Loss of information
If staining is performed to visualize tissue sections for identifying regions of interest, then phenotypic features can be observed, but the molecular information degrades
Solution Approach 1:
The tissue block is divided into multiple series of sections, with alternating sections allocated for staining/visualization and for molecular analysis. This segmentation allows phenotypic features to be visualized on stained sections while preserving molecular information on adjacent unstained sections, eliminating the trade-off between visualization and molecular preservation.
Solution Approach 2:
Multiple serial sections are created from the same tissue block, serving as copies of each other. These copies allow different analyses to be performed on different sections - staining on one set and molecular analysis on another - without degrading the original molecular information needed for genomic studies.
3Loss of information
If multiple biopsies are taken to capture tumor heterogeneity, then sub-clonal composition can be characterized, but the procedure becomes complex and time-consuming
Solution Approach 1:
The patent creates a three-dimensional spatial map of the tumor by assigning x, y, z coordinates to tissue sections and features. This 3D mapping allows comprehensive characterization of tumor heterogeneity within a single biopsy by sampling multiple (x, y, z) locations, eliminating the need for multiple separate biopsies while simplifying the procedure.
Solution Approach 2:
The tissue block is pre-sectioned into multiple serial sections with established coordinate systems before analysis. This preliminary action creates a ready-to-use three-dimensional framework that facilitates systematic sampling of multiple locations within the tumor, making heterogeneity characterization more efficient and less complex.
4Measurement precision
If serial sections are cut from the tissue block for analysis, then multiple regions can be examined, but the sections may become distorted and misaligned
Solution Approach 1:
Fiducial markers are embedded in the tissue block before sectioning. These markers are carried through all serial sections, providing reference points that enable accurate alignment and spatial registration of sections. This preliminary action prevents distortion-related misalignment by establishing a stable coordinate framework that persists through the sectioning process.
Solution Approach 2:
Fiducial markers serve as intermediaries between the tissue sections and the coordinate system. These markers are visible in both the histological images and the coordinate reference system, enabling precise spatial registration and alignment of multiple sections without being affected by tissue distortion.
Data Source
AI summary
Three dimensional tumor volume is analyzed spatially by genomics and transcriptomics, or both. Thin sections are cut with a microtome using a tape transfer technique so that the thin tissue sections remain without any distortion or deformation, in sequence relative to their position in the original tissue, so that a three-dimensional coordinate system can be anchored to each tissue section. Small samples of tissue are extracted or punched from very precise locations in the supports using the coordinate system as a grid, with known x,y,z location, and subjected to genomic sequencing. Sequence data is analyzed using the three dimensional coordinate system, so that the original tissue is thereby analyzed as a three dimensional system volume. At the same time, alternate tissue sections (or the same sections from which samples have been extracted with sample punches) can be subjected to staining and imaging to do histochemical analysis.